title: Hispolon induces apoptosis through JNK1/2-mediated activation of a caspase-8, -9, and -3-dependent pathway in acute myeloid leukemia (AML) cells and inhibits AML xenograft tumor growth in vivo.
abstract: Hispolon is an active phenolic compound of Phellinus igniarius, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML.
authors.affiliation: School of Medicine, ‡Institute of Biochemistry and Biotechnology, and §Institute of Medicine, Chung Shan Medical University , No. 110, Section 1, Chien-Kuo N Road, Taichung 40201, Taiwan.
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Hsiao
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Chow
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.forename: Chien-Huang
authors.initials: CH
authors.lastname: Lin
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
mesh_terms: D000363:Agaricales / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D002396:Catechols / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D002396:Catechols; D019253:Proto-Oncogene Proteins c-bcl-2; C103442:hispolon; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9